Combined elevation of AURKB and UBE2C predicts severe outcomes and therapy resistance in glioma

Wahafu, Alafate; Zuo, Jie; Deng, Zhong; Guo, Xiaoye; Wu, Wei; Zhang, Wei; Xie, Wei; Wang, Maode; Wang, Jia

doi:10.1016/j.prp.2019.152557

Cited by 26 publications

(26 citation statements)

References 44 publications

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“…a-j Kaplan-Meier curves showed that LGG patients with high expression of CDC20 (a), FN1 (b), AURKB (c), AURKA (d), KIF2C (e), BIRC5 (f), CCNB2 (g), UBE2C (h), CCNA2 (i), and CENPE (j) had reduced OS patients (Wang et al 2017;Zhang et al 2019). Aurora kinase B (AURKB) and ubiquitin-conjugating enzyme E2 C (UBE2C) are involved in the tumorigenesis of gliomas and other malignancies (Alafate et al 2019), and simultaneously elevated expression of AURKB and UBE2C is strongly correlated with poor prognosis and therapy resistance in glioma. Interactions between aurora kinase A (AURKA) and AURKB stabilize and protect AURKA/B from degradation, and AURKB is closely correlated with chemoresistance and radioresistance (Alafate et al 2019;Yu et al 2017).…”

Section: Discussionmentioning

confidence: 99%

Serine Incorporator 2 (SERINC2) Expression Predicts an Unfavorable Prognosis of Low-Grade Glioma (LGG): Evidence from Bioinformatics Analysis

Cui

Lei

et al. 2020

J Mol Neurosci

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Serine Incorporator 2 (SERINC2) is a transmembrane protein that incorporates serine into membrane lipids. The function of SERINC2 in tumors has been reported, but the role of SERINC2 in gliomas is not fully understood. RNA-sequencing data from The Cancer Genome Atlas (TCGA) (530 cases of low-grade glioma (LGG) and 173 cases of glioblastoma multiforme (GBM)) and microarray data from Gene Expression Omnibus (GEO) (Accession No. GSE16011, 284 cases gliomas were included) were acquired. Bioinformatics analysis was performed as the primary method to examine the function of SERINC2 and its correlated genes in glioma. SERINC2 was highly expressed in GBM compared with LGG and normal brain tissues. Elevated SERINC2 expression predicted shorter 5-, 10-, and 15-year overall survival (OS) of LGG patients and isocitrate dehydrogenase-1 (IDH-1) mutation-type LGG patients but had no effect on the OS of GBM patients. Cox regression analysis showed that SERINC2 was an independent factor in LGG OS. Methylation analysis found that 13 CpG methylation sites (methylation450k) correlated with SERINC2 expression in LGG. The mRNA expression level of SERINC2 was significant lower in the DNA deletion group than in the intact and amplification groups. A total of 390 copositive and 244 conegative correlation genes with SERINC2 were obtained from LGG in TCGA-LGG and GSE16011. Gene ontology (GO) category and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses showed that the copositive correlation genes were primarily enriched in the mitotic process and cell cycle. Combining the results from the protein-protein interaction (PPI) network of SERINC2 correlation genes and CytoHubba led to the selection of 10 hub genes (CDC20, FN1, AURKB, AURKA, KIF2C, BIRC5, CCNB2, UBE2C, CCNA2, and CENPE). OncoLnc analysis confirmed that high expression levels of these hub genes were associated with poor OS in LGG. Our results suggested that aberrant SERINC2 expression existed in glioma and that its expression might be a potential prognostic marker in LGG patients. CDC20, FN1, AURKB, AURKA, KIF2C, BIRC5, CCNB2, UBE2C, CCNA2, and CENPE may be potential biomarkers and therapeutic targets for LGG.

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Section: Discussionmentioning

confidence: 99%

Serine Incorporator 2 (SERINC2) Expression Predicts an Unfavorable Prognosis of Low-Grade Glioma (LGG): Evidence from Bioinformatics Analysis

Cui

Lei

et al. 2020

J Mol Neurosci

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“…Total RNA was extracted using RNeasy mini kits according to the manufacturer's instruction as previously described . Concentration of RNA was carefully determined by Nanodrop 2000.…”

Section: Methodsmentioning

confidence: 99%

“…Total RNA was extracted using RNeasy mini kits according to the manufacturer's instruction as previously described. 23 Concentration of RNA was carefully determined by Nanodrop 2000. GoldenstarTM RT6 cDNA Synthesis Kit (TsingKe Biotech) was used to synthesize cDNA strictly following the manufacturer's protocol.…”

Section: Quantitative Rt-pcr (Qrt-pcr)mentioning

confidence: 99%

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Elevation of CXCL1 indicates poor prognosis and radioresistance by inducing mesenchymal transition in glioblastoma

Wahafu

Zuo

et al. 2020

CNS Neurosci Ther

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Introduction Glioblastoma (GBM) is identified as a lethal malignant tumor derived from the nervous system. Despite the standard clinical strategy including maximum surgical resection, temozolomide (TMZ) chemotherapy, and radiotherapy, the median survival of GBM patients remains <15 months. Accumulating evidence indicates that rapid‐acquired radioresistance is one of the most common reasons for GBM recurrence. Therefore, developing novel therapeutic targets for radioresistant GBM could yield long‐term cures. Aims To investigate the functional role of CXCL1 in the acquired radioresistance and identify the molecular pathway correlated to CXCL1. Results In this study, we identified that CXCL1 is highly expressed in GBM and the elevation of CXCL1 is involved in radioresistance and poor prognosis in GBM patients. Additionally, silencing CXCL1 attenuated the proliferation and radioresistance of GBM cells. Furthermore, we demonstrated that CXCL1‐overexpression induced radioresistance through mesenchymal transition of GBM via the activation of nuclear factor‐kappa B (NF‐κB) signaling. Conclusion CXCL1 was highly enriched in GBM and positively correlated with poor prognosis in GBM patients. Additionally, elevated CXCL1 induced radioresistance in GBM through regulation of NF‐κB signaling by promoting mesenchymal transition in GBM.

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“…Immunohistochemistry was performed as previously described (31,32). Anti-PLK2 primary antibodies were purchased from Abcam (cat.…”

Section: Immunohistochemistry (Ihc)mentioning

confidence: 99%

Loss of PLK2 Induces Acquired Resistance to Temozolomide in GBM via Activation of Notch Signaling

Alafate

et al. 2020

Preprint

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BackgroundGlioblastoma (GBM) isa lethal type of primary brain tumor with a median survival less than 15 months.Despiting the recent improvements of comprehensive strategies,the outcomes for GBM patients remain dismal.Accumulating evidence indicates that rapid acquired chemoresistance is the major cause ofGBM recurrence thus leads to worse clinical outcomes. Therefore, developing novel biomarkers and therapeutic targets for chemoresistant GBM is crucial for long-term cures. MethodsTranscriptomic profiles of glioblastoma were downloaded from gene expression omnibus (GEO) and TCGA database. Differentially expressed genes were analyzed and candidate gene PLK2 was selected for subsequent validation. Clinical samples and corresponding data were collected from our center and measured using immunohistochemistry analysis. Lentiviral transduction and in vivo xenograft transplantation were used to validate the bioinformatic findings. GSEA analyses were conducted to identify potential signaling pathways related to PLK2 expression and further confirmed by in vitro mechanistic assays. ResultsIn this study, we identified PLK2 as an extremely suppressed kinase-encoding gene in GBM samples, particularly in therapy resistant GBM. Additionally, reduced PLK2 expression implied poor prognosis and TMZ resistance in GBM patients. Functionally, up-regulated PLK2 attenuated cell proliferation, immigration, invasion, and tumorigenesis of GBM cells. Besides, exogenous overexpression of PLK2 reduced acquired TMZ resistance of GBM cells. Furthermore, bioinformatics analysis indicated that PLK2 was negatively correlated with Notch signaling pathway in GBM. Mechanically, loss of PLK2 activated Notch pathway through negative transcriptional regulation of HES1 and degradation of Notch1.ConclusionLoss of PLK2 enhances aggressive biological behavior of GBM through activation of Notch signaling, indicating that PLK2 could be a prognostic biomarker and potential therapeutic target for chemoresistant GBM.

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Combined elevation of AURKB and UBE2C predicts severe outcomes and therapy resistance in glioma

Cited by 26 publications

References 44 publications

Serine Incorporator 2 (SERINC2) Expression Predicts an Unfavorable Prognosis of Low-Grade Glioma (LGG): Evidence from Bioinformatics Analysis

Serine Incorporator 2 (SERINC2) Expression Predicts an Unfavorable Prognosis of Low-Grade Glioma (LGG): Evidence from Bioinformatics Analysis

Elevation of CXCL1 indicates poor prognosis and radioresistance by inducing mesenchymal transition in glioblastoma

Loss of PLK2 Induces Acquired Resistance to Temozolomide in GBM via Activation of Notch Signaling

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